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| | ==Cryo-EM structure of NCP_THF2(-3)-UV-DDB== | | ==Cryo-EM structure of NCP_THF2(-3)-UV-DDB== |
| - | <StructureSection load='6r91' size='340' side='right'caption='[[6r91]], [[Resolution|resolution]] 4.10Å' scene=''> | + | <SX load='6r91' size='340' side='right' viewer='molstar' caption='[[6r91]], [[Resolution|resolution]] 4.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6r91]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R91 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6R91 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6r91]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R91 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R91 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.1Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6r91 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r91 OCA], [http://pdbe.org/6r91 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6r91 RCSB], [http://www.ebi.ac.uk/pdbsum/6r91 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6r91 ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene></td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6r91 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r91 OCA], [https://pdbe.org/6r91 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r91 RCSB], [https://www.ebi.ac.uk/pdbsum/6r91 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r91 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/DDB2_HUMAN DDB2_HUMAN]] Defects in DDB2 are a cause of xeroderma pigmentosum complementation group E (XP-E) [MIM:[http://omim.org/entry/278740 278740]]; also known as xeroderma pigmentosum V (XP5). XP-E is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities.<ref>PMID:8798680</ref> | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DDB1_HUMAN DDB1_HUMAN]] Required for DNA repair. Binds to DDB2 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also appears to function as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). May also play a role in ubiquitination of CDKN1B/p27kip when associated with CUL4 and SKP2.<ref>PMID:12732143</ref> <ref>PMID:15448697</ref> <ref>PMID:14739464</ref> <ref>PMID:15882621</ref> <ref>PMID:16260596</ref> <ref>PMID:16482215</ref> <ref>PMID:17079684</ref> <ref>PMID:16407242</ref> <ref>PMID:16407252</ref> <ref>PMID:16678110</ref> <ref>PMID:16940174</ref> <ref>PMID:17041588</ref> <ref>PMID:16473935</ref> <ref>PMID:18593899</ref> <ref>PMID:18381890</ref> <ref>PMID:18332868</ref> [[http://www.uniprot.org/uniprot/DDB2_HUMAN DDB2_HUMAN]] Required for DNA repair. Binds to DDB1 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also appears to function as the substrate recognition module for the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex DDB1-CUL4-ROC1 (also known as CUL4-DDB-ROC1 and CUL4-DDB-RBX1). The DDB1-CUL4-ROC1 complex may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. The DDB1-CUL4-ROC1 complex also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. Isoform D1 and isoform D2 inhibit UV-damaged DNA repair.<ref>PMID:14751237</ref> <ref>PMID:9892649</ref> <ref>PMID:10882109</ref> <ref>PMID:11278856</ref> <ref>PMID:11705987</ref> <ref>PMID:12732143</ref> <ref>PMID:12944386</ref> <ref>PMID:15882621</ref> <ref>PMID:16260596</ref> <ref>PMID:16678110</ref> <ref>PMID:16473935</ref> <ref>PMID:18593899</ref> [[http://www.uniprot.org/uniprot/H2B1J_HUMAN H2B1J_HUMAN]] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.<ref>PMID:11859126</ref> <ref>PMID:12860195</ref> <ref>PMID:15019208</ref> Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.<ref>PMID:11859126</ref> <ref>PMID:12860195</ref> <ref>PMID:15019208</ref> | + | [https://www.uniprot.org/uniprot/H31_HUMAN H31_HUMAN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6r91" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6r91" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[DNA damage-binding protein|DNA damage-binding protein]] |
| | + | *[[Histone 3D structures|Histone 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| - | </StructureSection> | + | </SX> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bunker, R D]] | + | [[Category: Bunker RD]] |
| - | [[Category: Cavadini, S]] | + | [[Category: Cavadini S]] |
| - | [[Category: Matsumoto, S]] | + | [[Category: Matsumoto S]] |
| - | [[Category: Thoma, N H]] | + | [[Category: Thoma NH]] |
| - | [[Category: 6-4 photoproduct]]
| + | |
| - | [[Category: Dna binding protein]]
| + | |
| - | [[Category: Dna damage]]
| + | |
| - | [[Category: Nucleosome]]
| + | |
| Structural highlights
Function
H31_HUMAN
Publication Abstract from PubMed
Access to DNA packaged in nucleosomes is critical for gene regulation, DNA replication and DNA repair. In humans, the UV-damaged DNA-binding protein (UV-DDB) complex detects UV-light-induced pyrimidine dimers throughout the genome; however, it remains unknown how these lesions are recognized in chromatin, in which nucleosomes restrict access to DNA. Here we report cryo-electron microscopy structures of UV-DDB bound to nucleosomes bearing a 6-4 pyrimidine-pyrimidone dimer or a DNA-damage mimic in various positions. We find that UV-DDB binds UV-damaged nucleosomes at lesions located in the solvent-facing minor groove without affecting the overall nucleosome architecture. In the case of buried lesions that face the histone core, UV-DDB changes the predominant translational register of the nucleosome and selectively binds the lesion in an accessible, exposed position. Our findings explain how UV-DDB detects occluded lesions in strongly positioned nucleosomes, and identify slide-assisted site exposure as a mechanism by which high-affinity DNA-binding proteins can access otherwise occluded sites in nucleosomal DNA.
DNA damage detection in nucleosomes involves DNA register shifting.,Matsumoto S, Cavadini S, Bunker RD, Grand RS, Potenza A, Rabl J, Yamamoto J, Schenk AD, Schubeler D, Iwai S, Sugasawa K, Kurumizaka H, Thoma NH Nature. 2019 May 29. pii: 10.1038/s41586-019-1259-3. doi:, 10.1038/s41586-019-1259-3. PMID:31142837[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Matsumoto S, Cavadini S, Bunker RD, Grand RS, Potenza A, Rabl J, Yamamoto J, Schenk AD, Schubeler D, Iwai S, Sugasawa K, Kurumizaka H, Thoma NH. DNA damage detection in nucleosomes involves DNA register shifting. Nature. 2019 May 29. pii: 10.1038/s41586-019-1259-3. doi:, 10.1038/s41586-019-1259-3. PMID:31142837 doi:http://dx.doi.org/10.1038/s41586-019-1259-3
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